NMR is probably the most powerful and widely used analytical technique for structure determination and function elucidation of molecules of all types, but it suffers from low sensitivity, particularly for insoluble biological macromolecules. Dynamic Nuclear Polarization (DNP) with Magic Angle Spinning (MAS) has recently demonstrated signal to noise (S/N) gains exceeding two orders of magnitude at ˜100 K compared to conventional MAS-NMR in many biological solids.
It is important at the outset to distinguish between two very different NMR techniques often just called DNP for short. There is dissolution-DNP and non-dissolution DNP, the latter of which has usually been the subset of methods classified as MAS-DNP at ˜100 K. The novel resonator disclosed herein is expected to be relevant to non-dissolution DNP.
Briefly, the dissolution method permits increased S/N in MRI and in NMR of liquids by hyperpolarizing an agent at a low temperature (usually below 4 K) by irradiation at the electron paramagnetic resonance (EPR) frequency in a lower-field magnet (usually 1 to 3.5 T); and then quickly heating (and melting) it, and rapidly transporting it to and injecting it into an animal or a liquid sample in a higher field magnet (usually 3-21 T) several meters away, where the NMR methods are carried out in a completely separate NMR detection system in the few tens of seconds available before the hyperpolarization decays.
In non-dissolution methods, microwave (MW—note the common non-SI abbreviation) irradiation, or more properly millimeter-wave (mmw) irradiation takes place within the same resonator as the NMR detection—at the same field, and almost always at the same temperature (though there have been a few attempts to cycle the temperature between the mmw and the NMR events).
In non-dissolution high-field DNP methods, it is advantageous to utilize a resonator design that achieves high efficiency at the mmw frequency (typically 190 to 600 GHz) and at the several NMR frequencies (typically 30 to 900 MHz) simultaneously. A primary cavity design objective then would be to obtain the highest possible efficiency in generation of EPR B1S throughout a moderately lossy sample of sufficient volume in a way that it can also be very efficiently irradiated with intense rf fields at two or three NMR frequencies. Yet, no previous multi-tuned DNP experiments have utilized cavities, and the 1H nanoliter-volume DNP experiments where micro cavities have been utilized (on samples much to small to be useful for most purposes) showed poor baseline NMR performance in S/N and poor spectral resolution.
Detailed simulations of the novel Doty DNP cavity using state-of-the-art microwave simulation software (COMSOL), along with preliminary validation experiments, have shown the potential for achieving the needed electron spin saturation in large samples from mmw irradiation with about two orders of magnitude lower MW power than seen in existing MAS-DNP designs for samples of similar volume (0.1-10 μL) and sample conductivity σs (0.1-1 S/m) at the same B0 and temperature.
It has often been stated that MAS-DNP will permit four orders of magnitude reduction in signal acquisition time in many solids NMR applications. Granted, that may be a bit of hyperbole—mostly because of unavoidable concomitant changes in spectral linewidth (1/T2*), spin-lattice relaxation time (T1), sample volume, sample dilution (from the matrix and polarizing agent), and sample preparation and changing difficulties. Still, the DNP promise is enormous, as witnessed by the exponential growth in solids-DNP publications over the past four years.
Despite the enormous potential benefit, the adaptation rate of MAS-DNP has been severely limited by its very high price tag (currently $1.8-4M). The driver of the exceedingly high price for existing DNP capabilities is the “need” for a gyrotron. The gyrotron has been believed to be the only mmw source capable of providing the power levels required for the desired DNP methods. The novel resonator disclosed herein will render, in many cases, the gyrotron to be unnecessary by allowing for much less expensive low-power solid-state sources. At the same time, it will enable the use of much larger sample volumes with multi-tuned multi-nuclear (H/X/Y/e−) circuits that have much higher efficiency and S/N.
The focus of the resonator design disclosed herein is for static DNP experiments—non-spinning and non-dissolution. This is an area that has thus far received much less attention than MAS-DNP. Preliminary simulations suggest that extensions of some of the concepts disclosed herein may also permit dramatic increases in efficiency of MAS-DNP, and such innovations are expected to be the subject of a future patent application.
While the novel tunable DNP cavity disclosed herein is directly compatible only with static DNP methods, the samples can be solids, liquids, or semi-solids. Granted, the linewidths from static solids NMR techniques are always much greater than in MAS. However, static high-power NMR methods have been similarly successful in yielding structures of large, complex, helical membrane proteins from the correlated dipolar and anisotropic chemical shift data such methods uniquely provide [1].
Thin glass plates were initially used to achieve the protein alignment needed to obtain high resolution of membrane proteins in lipid bilayers. Another option is to insert the proteins into large bicelles, which are magnetically anisotropic and thus self-align when placed in solution in an external magnetic field [2]. While bicelles provide a native-like environment for the incorporated membrane proteins [3, 4], their composition is restricted to a very limited repertoire of lipids. As an alternative, it has been shown that anodic aluminum oxide (AAO) nanopores can readily be fabricated that provide highly homogeneous and ordered nano-templates for aligning an exceptionally broad range of lipids [5, 6]. Such nanoporous substrates provide the very large surface area required for the NMR studies, and have additional advantages with respect to control of the biophysical environment and improving microwave efficiency in the novel cavity, as will become clear later.
While dissolution DNP methods can be applied to lossy liquid samples near room temperature (RT), they are not likely to be very useful for structure determination of macromolecules, and they come with major complications—not the least of which are the requirements of a second superconducting magnet, sub-4-K cooling of the polarizing agent, the rapid shuttling and heating systems, and the poor compatibility with time averaging.
On the other hand, non-dissolution DNP is not easily applied to lossy liquid samples near RT, largely because electron T1's are usually several orders of magnitude shorter than those of 1H. Hence, much higher B1S is required to saturate the electron spins. At the same time, the effective sample conductivity at RT may be five times higher than that at 100 K, further exacerbating the microwave heating problem. This is a major limitation of DNP, since most structure determinations utilize liquids methods. When available methods are applied to very large macromolecules at low concentrations, the signal acquisition time can still be measured in weeks, even at 21 T. It could be quite beneficial if DNP enhancements could be effectively applied to real problems in liquids NMR methods. Unfortunately, the spectral resolution of MAS-DNP in frozen solutions at 100 K is usually two orders of magnitude worse than required by liquids methods.
Substantial gains in S/N from high-field DNP have been demonstrated in liquids above RT at 9.2 T, but only for single-resonance 1H NMR in sample volumes in the range of 3-100 nL—and with very poor spectral resolution [7, 8]. In one case, a factor of 30 gain in S/N was demonstrated with a B1s of 640 μT [7], but in the other case, a factor of 80 gain was seen with the more practical B1S of only 350 μT [8]. If significant biological applications of DNP are to be realized in lossy liquid samples, it will be necessary to dramatically reduce the mean ratio of E/B1S within the sample while simultaneously addressing the issues of achieving very high B0 homogeneity, efficient triple resonance rf, and effective heat removal from the unavoidable microscopic hot spots within samples of useful size (several μL). All of these issues can be more optimally addressed in the cavity disclosed herein, thereby enabling “high resolution” DNP-NMR in liquid samples near RT. Indeed, resolution will still be more than an order of magnitude away from state-of-the-art liquids NMR resolution, but sometimes an order of magnitude better than seen in MAS-DNP at 100 K.
Prior DNP Resonators. Nanni et al reported achieving B1S of ˜25 μT (corresponding to ˜0.73 MHz γB1S) for 4 W (incident onto the rf coil) at 250 GHz in a 4 mm rotor over a short sample length, for which a factor-of-100 gain in S/N was observed for a particular example at ˜100 K [9]. They also show a curve for enhancement vs field strength, from which one deduces that half of this microwave field strength (i.e., ˜1 W incident power) would give a DNP enhancement factor ∈DNP of ˜50. The typical frozen sample has been reported to have relative permittivity ∈r=3.5 at 140 GHz and 77 K, with loss tangent of 0.005 [9], which would be equivalent to a conductivity σs of 0.14 S/m. The figures in their papers show the microwaves being launched from a horn transversely onto the rf coil that surrounds the rotor. They show results of a single-pass analytical model and a highly simplified HFSS simulation, both of which assume there is no cavity or resonator effect at the MW frequency. They reported MW conversion factor gMW of ˜12 μT/W1/2, though for an unclear sample volume. Their models suggest the sample volume receiving substantial irradiation in this 1H/13C/15N/e− MAS-DNP probe [10] may have been about 6 μL, though our more detailed simulations indicated a much larger sample—perhaps 25 μL—was being well irradiated, for which the time-averaged B1S was much more uniform than seen from their models.
Details of commercially available MAS-DNP probes do not seem to be publicly available, but those by Bruker (the only current commercial supplier of complete MAS-DNP systems) are widely known to be heavily based on collaborations with the Griffin group at MIT, and the information that is available indicates their MW performance is similar to that reported in the above and other publications from the MIT group.
Prisner and Denysenkov disclose in WO 2009/12160 a micro “Fabry-Perot” resonator built on a reflective rf stripline with an effective sample volume of ˜0.1 μL. (We note that “Fabry-Perot” is not very descriptive, and the term has been applied loosely to a wide range of types of resonators.) They reported achieving MW conversion factor 370 μT/W1/2 at 260 GHz for a 100 mM saline solution near RT, where the sample conductivity would be ˜1 S/m [11, 12]. The loaded Q of the microwave resonator was ˜200. The ultra-low inductance of the stripline used for the 1H resonator would make efficient double-tuning of such a coil (for example, for 1H/15N) impractical. Moreover, the sample volume is a factor of 10-200 below what would be needed for sufficient S/N for 3D NMR structure determination methods to be practical on macromolecules, and their spectral resolution (˜0.1 ppm) was an order of magnitude worse than what is desired. It appears that their stripline generated a 25 μs π/2 pulse for 1H at 1 W at 392 MHz.
Neugebauer, Prisner et al report gMW up to 450 μT/W1/2 at 260 GHz using a small helical resonator with sample volume up to 3 nL and a loaded Q up to 400 [12]. Here, the sample volume is three orders of magnitude smaller than needed for insensitive nuclides and the spectral resolution was ˜0.3 ppm.
Feintuch, Goldfarb et al report up to 830 kHz (˜29 μT) at ˜0.3 W, or gMW ˜50 μT/W1/2 at 95 GHz using a horn-mirror-Helmholtz arrangement with a total sample volume of ˜30 μL [13]. In this case, the rf coil was well outside the microwave region, so rf performance was very poor by conventional standards. It appears that it probably required ˜500 W to achieve a 1H n/2 of 3 μs (˜2 mT), though the reporting was not clear. The fraction of the sample actually experiencing something close to the peak MW transverse magnetic field was not reported. An estimate is that probably 5-10 μL was seeing 25-35 μT B1S at 0.3 W of incident MW power.
In U.S. Pat. No. 7,292,035, Habara and Park disclose the use of a sample tube co-axially inside a leaky “Fabry-Perot” type cavity formed by two concave mirrors with a micro-solenoid surrounding the confocal space between them [14]. The disclosure envisions the use of a 3-mm glass sample tube at 200 GHz, with mirrors and solenoid about an order of magnitude larger in diameter. No performance calculations or data are provided, but an estimate based on analogy to work by the Prisner group is that perhaps gMW up to ˜20 μT/W1/2 could be expected. However, the poor performance of the NMR rf coil (in either embodiment) would lead to very poor DNP performance.
In patent application publication US 2009/0121712, Han et al disclose a method of obtaining improved sensitivity on boundary layer water interacting with interfacial molecular assemblies by attaching a nitroxide to a surface layer to permit DNP enhancement of the surface water [15]. In experiments at 4.2 K, this group irradiated a 50-μL sample in a polyethylene cup from the end of a 5.3 mm corrugated waveguide at 200 GHz. A mirror on the opposite side of the sample reflected most of the transmitted microwaves back through the sample, but otherwise there was no attempt at confinement [16]. Apparently, no attempt was made by the inventors to determine a conversion factor, but an estimate based on relative dimensions and other considerations is that the average value was probably less than that obtained by Nanni et al.
In WO 2013/057688, Macor et al disclose the use of a photonic band gap (PBG) resonator fed co-axially with BO by a corrugated waveguide with a co-axial central sample tube surrounded by a birdcage resonator for the rf [17]. This represents one of the first highly innovative attempts to use a mmw resonator with an rf resonator in a way that may permit significant advantages compared to variations on the brute-force methods from the 1970's (Yannoni, Wind, Maciel, and others). No conversion factors for any of the Macor embodiments were reported. Our simulations showed the potential of such resonators to achieve substantial improvement in gMW, but at the expense of many of the other DNP cavity design objectives listed further down in this background material.
Pike et al show a method of axial microwave irradiation at 187 GHz in MAS-DNP by means of quasi-optical mirrors mounted on an essentially standard Doty MAS NMR probe [18]. This illustrates a MW feed method that could reduce some of the challenges associated with the PBG resonator by Macor et al. Again, conversion factors were not reported, but rough simulations indicated somewhat higher gMW than reported by Nanni et al.
In WO 2013/000508, Annino et al disclose novel structures suitable for double resonance at the MW (EPR) frequency and at an rf (NMR) frequency with certain advantages for very thin samples, including arrays of such [19]. In particular, the inventions could be compatible with simultaneous and uniform irradiation by visible or UV light, microwaves, and rf. This could be advantageous for photo-CIDNP, which permits hyperpolarization at room temperature and without paramagnetic centers in the sample, thereby extending the relaxation time of the polarized protons. The inventors also present an excellent overview of the challenges of many of the prior DNP probe heads.
There are rf (discussed later) and other problems with the Annino invention, some of which include the following. There is a failure to appreciate that variable effects in the sample size and its dielectric properties will radically change the MW mode structure, S11, and efficiency relative to that seen for a particular idealized simulation, and anti-reflective coatings will not solve this problem. The susceptibility broadening effects from the grid and flow channels will be substantial, and composite construction will not solve this issue at the scale envisioned.
While the Annino invention could offer the advantage of much better MW field uniformity than generally seen in other DNP probe heads, it should be pointed out that many prior DNP probe heads with quite non-uniform MW fields have worked very well with respect to ∈DNP. Uniformity of the MW field is apparently not a significant issue in most of the DNP methods that have been developed. Again, apparently, no attempt was made by the inventors to determine a conversion factor for any of the Annino embodiments. The fact that the inventors anticipate an advantage from placing the grid structure inside a confocal Fabry Perot resonator seems to confirm a crude estimate which suggests its gMW in practice will usually not be much better than ˜20 μT/W1/2, primarily because of the enormous practical difficulty of obtaining low S11 with such resonators when real samples are present.
NMR and EPR S/N Theory. From the classic works, the NMR or EPR S/N from a single 90° pulse at thermal equilibrium with quadrature reception is given by [20]:
                              S          /          N                =                                            1000              [                                                                    η                    2                                    ⁢                                                            2                      ⁢                                                                                          ⁢                      π                      ⁢                                                                                          ⁢                                              μ                        0                                                                                                              12                  ⁢                                                                          ⁢                                      k                                          B                      ⁢                                                                                                                                  3                      ·                      2                                                                                  ]                        [                                                            n                  S                                ⁢                γ                ⁢                                                                  ⁢                                                      I                    x                                    ⁡                                      (                                                                  I                        x                                            +                      1                                        )                                                  ⁢                                                      T                    2                    *                                                                                                T                  S                                ⁢                                                                            T                      R                                        +                                          T                      P                                                                                            ]                    ⁢                                    (                                                η                  E                                ⁢                                  η                  F                                ⁢                                  Q                  L                                ⁢                                  V                  S                                            )                                      1              ·              2                                ⁢                      ω                          3              ·              2                                                          (        1        )            where ns is the number of spins per mL at resonance in the spectral line, T2* is calculated from the actual linewidth, TS is the sample temperature, TR is the weighted average temperature of the circuit coils and capacitors, TP is the effective preamp noise temperature, ηE is the rf circuit efficiency, ηF is the magnetic filling factor, QL is the loaded and matched circuit quality factor, VS is the sample volume [mL], and ω is the Larmour precession frequency, γB0. (See reference for more details and definitions [20].) Note, that the derivations here work for both nuclear spins and electron spins. For example, γ=1.76E11/s/T for e−, γ=2.68E8/s/T for 1H, and γ=2.7E7/s/T for 15N.
Most prior DNP work has not paid sufficient attention to maximizing ηF, T2*, ηE, and VS, or to minimizing TR. Part of the reason is that prior to the advent of modern full-wave EM software, it has been very difficult to accurately determine magnetic filling factor,
                              η          f                =                                            ∫              s                        ⁢                                          B                1                2                            ⁢              d              ⁢                                                          ⁢              V                                            2            ⁢                                                  ⁢                          μ              0                        ⁢            U                                              (        2        )            where U is the total peak magnetic energy at resonance, B1 is the transverse component of the rotating component of the rf (or mmw) magnetic field, and the integration in the numerator is over the sample space. The following equivalent expression for S/N can be derived for cases where B1 is reasonably uniform throughout the sample:
                              S          /          N                =                              1000            [                                                            η                  2                                ⁢                π                ⁢                                                      10                    ⁢                                                                                  ⁢                                          µ                      0                                                                                                  48                ⁢                                                                  ⁢                                  k                  B                                      3                    ·                    2                                                                        ]                    [                                                    n                S                            ⁢                                                I                  x                                ⁡                                  (                                                            I                      x                                        +                    1                                    )                                            ⁢                              V                S                            ⁢                              ω                2                            ⁢                                                T                  2                  *                                                                                    τ                90                            ⁢                              T                S                            ⁢                                                P                  ⁡                                      (                                                                  T                        R                                            +                                              T                        P                                                              )                                                                                ]                                    (        3        )            where P is the power required to achieve a π/2 pulse length of τ90. Of course, equations 1 and 3 give identical results (where the latter is valid), and in either case a correction factor of ≈0.7 is required for linear polarization. For EPR (and hence for DNP) equation 1 is more useful—because it will generally not be possible to achieve anything close to uniform B1 throughout the sample. The required integrations can be carried out in modern E&M software such as COMSOL RF, and presumably in some other competitive products such as HFSS, CST, Remcom, Maple, FEKO, etc. For the DNP cavity with the port relative reflected power S11 expressed in dB, an appropriate definition of what is called “rf efficiency” in the multi-tuned rf circuit would beηE=1−10S11·10  (4)
DNP Cavity Optimization. As noted earlier, the primary objective in DNP cavity design is to generate the highest possible efficiency in producing B1S (at the EPR frequency) throughout a moderately lossy sample of sufficient volume in a way that it can also be very efficiently irradiated with intense rf fields at two or three NMR frequencies. From the above equations, it can be shown that the appropriate mmw cavity optimization Figure of Merit, FOM, isFOM=ηFQLVS(1−|S11|)  (5)
While others have not generally published ηE, ηF, QL, S11, or FOM for their DNP cavities, a few have published maximum B1S (or equivalent) at incident mmw power P. From eq. (3) and other well known relationships, the following can be derived for cases where an effective mean B1S is known over the active VS:
                              F          ⁢                                          ⁢          O          ⁢                                          ⁢          M                =                                            η              E                        ⁢                          η              F                        ⁢                          Q              L                                =                                    5              ⁢                                                          ⁢              ω              ⁢                                                          ⁢                              V                S                            ⁢                              B                                  1                  ⁢                  S                                2                                                    4              ⁢                                                          ⁢              π              ⁢                                                          ⁢              P                                                          (        6        )            From estimates of the effective mean B1S over the active VS, an FOM can then be estimated for some published DNP cavities, as seen later in Table 1.
Detailed COMSOL simulations indicate the Doty tunable DNP cavities can have FOM 20-2000 times what is seen in the prior art. (Note: EPR S/N would be proportional to the square root of the above FOM at a given B0.)
Circular polarization is certainly useful in MRI. However, circular polarization is generally not used in NMR or in conventional EPR because much more gain in S/N can be achieved by focusing on efficient linear polarization, even when sample losses dominate. The arguments for linear polarization appear to be even stronger for mmw resonators, where it appears to be impractical to incorporate lumped phase shifters (as used in MRI) around the sample at distances small compared to the wavelength within the sample.
Static tunable DNP cavity optimization boils down to the following objectives:    1. The cavity network should achieve maximum mmw FOM (with perhaps some tradeoffs to improve ηF at the expense of QL and even FOM) at low mmw S11 for a wide range of sample sizes and dielectric properties.    2. The design should be compatible with an rf coil of high ηF and suitable inductance (15-150 nH) to permit high NMR S/N (as quantified by eq. 1 or eq. 3) in triple-resonance NMR experiments.    3. The microwave tuning/matching system needs to allow the user to easily and quickly adjust for low S11 at the mmw input port for a wide range of sample sizes, conductivities, and permittivities, both at RT and when the sample is cold inside the magnet, where the sample properties may be very different.    4. It should be reasonably easy for the user to prepare and load samples of various types, into practical sample holders, with sample volumes ranging from 0.01 μL to perhaps even 50 μL at lower fields.    5. Since the sample holders, containers, and their plugs will always constitute a substantial part of the mmw resonant system, it must be practical to reproduce them from suitable materials with high precision at reasonable cost.    6. The design needs to be compatible with all of the conventional NMR and variable temperature (VT) requirements—from perhaps 350 K at least down to 80 K and preferably down to 20 K.    7. It should be practical to manufacture to a very high degree of approximation what is simulated.    8. The design should be able to be scaled for use at all common fields from 6.5 T to 35 T.    9. It should be easy to clean the cavity very thoroughly to eliminate contamination background signals in case of sample leakage.    10. It should be possible to achieve reasonably high microwave B1 homogeneity of predicted magnitude over a sufficiently small sample if it is properly situated.
DNP RF Optimization. The primary focus of the background discussion thus far has been on the mmw side of the design problem, partly because that is what is seen mostly in the patent and professional literature on DNP probe heads—very little attention is usually paid to rf optimization issues, and with predictable results. While rf optimization issues have been well understood by some NMR probe builders for two decades [20], many key issues for maximizing NMR S/N have been ignored in most of the non-dissolution DNP prior art.
The Prisner and Denysenkov approach [7, 11] suffers particularly from extremely small sample volume (˜80 nL), very poor 1H ηF (they required 1 W to achieve a 25 μs π/2 with a nano-sample), poor spectral resolution (0.1 ppm), and incompatibility with even fixed multi-resonance rf tuning (e.g., 1H/13C). The Feintuch and Goldfarb approach [13] with a much larger sample at low field (3.4 T) still has very poor 1H ηF (they apparently required ˜500 W to achieve a 3 μs π/2). The Habara and Park approach [14] would appear to have even worse 1H ηF, though data are not reported. The Han/Armstrong approach [15] could be adapted to efficient H/X/Y rf (following methods used in the design of liquids NMR probes), but their mmw design has severe limitations with respect to mmw FOM and conversion factor.
Macor et al anticipate the use of many types of rf coils inside their PBG resonator, but they fail to appreciate how difficult it will be to support, tune, and feed the coils without drastically perturbing the desired PBG resonant mode. The rf coil will require very long leads, severely compromising ηE in H/X/Y tuning. They show axial mmw irradiation in their PBG resonator, which is probably the only viable option but presents major challenges in sample access.
The Annino novel structures [19] come with what will be show-stopper rf problems in their practical implementation for many applications. The inductance of the parallel-wire rf grid is about two orders of magnitude smaller than what is needed (20-100 nH) for efficient H/X/Y rf tuning. It appears that in one preferred embodiment, the rf parallel wire grid structure would be supported on a micro-tray (apparently ignored in the simulations) that holds the micro-sized planar sample between the rf coil structure and the mirror. For satisfactory rf performance, the rf grid would need to make repeatable contacts with the rest of the structure, with variations in contact resistance and inductance in the micro-ohm and pico-henry range—two orders of magnitude smaller that what is generally considered practical.
The biggest problem with single-tuned rf designs that achieve poor 1H ηF is that any attempt to extend such a design to H/X/Y (as is essential if DNP is to be fruitful in complex structure determinations) will be disastrous—from the perspectives of both maximum rf field strengths and S/N on the X and Y channels.
The Griffin/Nanni circuit [9, 10] is one of the better solids DNP rf circuits from a S/N perspective, but it still suffers from poor efficiency and high noise temperature on the mid-frequency (MF) and low-frequency (LF) channels for 1H/13C/15N (though it performs very well on 1H). The Doty circuit used in the approach by Pike et al [18] is better in these respects, but the Wylde mmw design used there has operational challenges.
For larger samples at high fields, there are strong arguments favoring dual-coil approaches for H/X/Y tuning in solids NMR probes—having the 1H on a cross coil and the X/Y on a solenoid [21, 22, 23]. For small samples, the arguments favor tuning a single solenoid to all three frequencies. As the focus of static DNP will usually be on smaller samples, the latter approach may usually be preferred. The losses in rf QL arising from the inner mmw cavity also weigh toward the “single-coil” approach. A number of circuits have been used satisfactorily [10, 22], and others will probably be reported in the near future. However, the dual-coil approach (usually an inner solenoid and an outer cross coil [23]) are likely to be preferred in some high-field cases, and the inventive mmw cavity will work splendidly with such.
Laminate reflective shields have been used for nearly three decades in MRI to provide high reflectivity at the MR coil frequencies (typically 64-600 MHz) while achieving very high transparency at the frequencies present in the gradient coil waveforms (mostly 20-3000 Hz). Obviously, six orders of magnitude separate 300 Hz and 300 MHz, so their rf skin depths δ differ by three orders of magnitude. The early methods simply relied on a continuous rf shield that was at least 2δ thick at the rf frequency. This was later found to not have sufficient transparency to the gradient waveforms under some conditions, and composites of overlapping copper patches were found to permit much better transparency at the gradient frequencies with little degradation in reflectivity at the rf frequency, as disclosed by Hayes in U.S. Pat. No. 4,642,569 [24], and later improved by Alecci and Jezzard [25].